Dietary lipids, already an important source of energy for tiny preemies, also provide a much-needed brain boost by significantly increasing global brain volume as well as increasing volume in regions involved in motor activities and memory, according to research presented during the Pediatric Academic Societies 2019 Annual Meeting.

“Compared with macronutrients like carbohydrates and proteins, lipid intake during the first month of life is associated with increased overall and regional brain volume for micro-preemies,” says Catherine Limperopoulos, Ph.D., director of MRI Research of the Developing Brain at Children’s National and senior author. “Using non-invasive magnetic resonance imaging, we see increased volume in the cerebellum by 2 weeks of age. And at four weeks of life, lipids increase total brain volume and boost regional brain volume in the cerebellum, amygdala-hippocampus and brainstem.”

The cerebellum is involved in virtually all physical movement and enables coordination and balance. The amygdala processes and stores short-term memories. The hippocampus manages emotion and mood. And the brainstem acts like a router, passing messages from the brain to the rest of the body, as well as enabling essential functions like breathing, a steady heart rate and swallowing.

According to the Centers for Disease Control and Prevention, about 1 in 10 U.S. babies is born preterm, or before 37 weeks gestation. Regions of the brain that play vital roles in complex cognitive and motor activities experience exponential growth late in pregnancy, making the developing brains of preterm infants particularly vulnerable to injury and impaired growth.

Children’s research faculty examined the impact of lipid intake in the first month of life on brain volumes for very low birth weight infants, who weighed 1,500 grams or less at birth. These micro-preemies are especially vulnerable to growth failure and neurocognitive impairment after birth.

The team enrolled 68 micro-preemies who were 32 weeks gestational age and younger when they were admitted to Children’s neonatal intensive care unit during their first week of life. They measured cumulative macronutrients – carbohydrates, proteins, lipids and calories – consumed by these newborns at 2 and 4 weeks of life. Over years, Limperopoulos’ lab has amassed a large database of babies who were born full-term; this data provides unprecedented insights into normal brain development and will help to advance understanding of brain development in high-risk preterm infants.

“Even after controlling for average weight gain and other health conditions, lipid intake was positively associated with cerebellar and brainstem volumes in very low birthweight preterm infants,” adds Katherine M. Ottolini, the study’s lead author.

According to Limperopoulos, Children’s future research will examine the optimal timing and volume of lipids to boost neurodevelopment for micro-preemies.

Pediatric Academic Societies 2019 Annual Meeting presentation

“Early lipid intake improves brain growth in premature infants.”

Saturday, April 27, 2019, 1:15-2:30 p.m. (EST)

Katherine M. Ottolini, lead author; Nickie Andescavage, M.D., Attending, Neonatal-Perinatal Medicine and co-author; Kushal Kapse, research and development staff engineer and co-author; and Catherine Limperopoulos, Ph.D., director of MRI Research of the Developing Brain and senior author, all of Children’s National.

“Proton magnetic resonance spectroscopy, a non-invasive imaging technique that describes the chemical composition of specific brain structures, enables us to measure metabolites that may play a critical role for growth and explain what makes breastfeeding beneficial for newborns’ developing brains,” says Catherine Limperopoulos, Ph.D.

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Micro-preemies who primarily consume breast milk have significantly higher levels of metabolites important for brain growth and development, according to sophisticated imaging conducted by an interdisciplinary research team at Children’s National.

“Our previous research established that vulnerable preterm infants who are fed breast milk early in life have improved brain growth and neurodevelopmental outcomes. It was unclear what makes breastfeeding so beneficial for newborns’ developing brains,” says Catherine Limperopoulos, Ph.D., director of MRI Research of the Developing Brain at Children’s National. “Proton magnetic resonance spectroscopy, a non-invasive imaging technique that describes the chemical composition of specific brain structures, enables us to measure metabolites essential for growth and answer that lingering question.”

The research-clinicians enrolled babies who were very low birthweight (less than 1,500 grams) and 32 weeks gestational age or younger at birth when they were admitted to Children’s neonatal intensive care unit in the first week of life. The team gathered data from the right frontal white matter and the cerebellum – a brain region that enables people to maintain balance and proper muscle coordination and that supports high-order cognitive functions.

Each chemical has its own a unique spectral fingerprint. The team generated light signatures for key metabolites and calculated the quantity of each metabolite. Of note:

And the percentage of days infants were fed breast milk was associated with significantly greater levels of both creatine and choline, a water soluble nutrient.

“Key metabolite levels ramp up during the times babies’ brains experience exponential growth,” says Katherine M. Ottolini, the study’s lead author. “Creatine facilitates recycling of ATP, the cell’s energy currency. Seeing greater quantities of this metabolite denotes more rapid changes and higher cellular maturation. Choline is a marker of cell membrane turnover; when new cells are generated, we see choline levels rise.”

Already, Children’s National leverages an array of imaging options that describe normal brain growth, which makes it easier to spot when fetal or neonatal brain development goes awry, enabling earlier intervention and more effective treatment. “Proton magnetic resonance spectroscopy may serve as an important additional tool to advance our understanding of how breastfeeding boosts neurodevelopment for preterm infants,” Limperopoulos adds.

Babies born prematurely – before 37 weeks of pregnancy – often have a lot of catching up to do. Not just in size. Preterm infants typically lag behind their term peers in a variety of areas as they grow up, including motor development, behavior and school performance.

New research suggests one way to combat this problem. The study, led by Children’s researchers and presented during the Pediatric Academic Societies 2018 annual meeting, suggests that the volume of carbohydrates, proteins, lipids and calories consumed by very vulnerable premature infants significantly contributes to increased brain volume and white matter development, even though additional research is needed to determine specific nutritional approaches that best support these infants’ developing brains.

During the final weeks of pregnancy, the fetal brain undergoes an unprecedented growth spurt, dramatically increasing in volume as well as structural complexity as the fetus approaches full term.

One in 10 infants born in the U.S. in 2016 was born before 37 weeks of gestation, according to the Centers for Disease Control and Prevention. Within this group, very low birthweight preemies are at significant risk for growth failure and neurocognitive impairment. Nutritional support in the neonatal intensive care unit (NICU) helps to encourage optimal brain development among preterm infants. However, their brain growth rates still lag behind those seen in full-term newborns.

“Few studies have investigated the impact of early macronutrient and caloric intake on microstructural brain development in vulnerable preterm infants,” says Katherine Ottolini, lead author of the Children’s-led study. “Advanced quantitative magnetic resonance imaging (MRI) techniques may help to fill that data gap in order to better direct targeted interventions to newborns who are most in need.”

The research team at Children’s National Health System enrolled 69 infants who were born younger than 32 gestational weeks and weighed less than 1,500 grams. The infants’ mean birth weight was 970 grams and their mean gestational age at birth was 27.6 weeks.

The newborns underwent MRI at their term-equivalent age, 40 weeks gestation. Parametric maps were generated for fractional anisotropy in regions of the cerebrum and cerebellum for diffusion tensor imaging analyses, which measures brain connectivity and white matter tract integrity. The research team also tracked nutritional data: Grams per kilogram of carbohydrates, proteins, lipids and overall caloric intake.

“We found a significantly negative association between fractional anisotropy and cumulative macronutrient/caloric intake,” says Catherine Limperopoulos, Ph.D., director of Children’s Developing Brain Research Laboratory and senior author of the research. “Curiously, we also find significantly negative association between macronutrient/caloric intake and regional brain volume in the cortical and deep gray matter, cerebellum and brainstem.”

Because the nutritional support does contribute to cerebral volumes and white matter microstructural development in very vulnerable newborns, Limperopoulos says the significant negative associations seen in this study may reflect the longer period of time these infants relied on nutritional support in the NICU.

“As a community-focused health system, one of our central missions is to train a new generation of residents to create successful community partnerships and integrate public health concepts into the everyday practice of medicine to improve the health of underserved communities,” says Cara Lichtenstein, M.D., MPH.

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The Children’s National Community Health Track (CHT) has been recognized by the Academic Pediatric Association with its prestigious Teaching Program Award. The honor was made public at the Pediatric Academic Societies (PAS) annual meeting on May 7, 2018 in Toronto, Ontario. The purpose of the award is to foster interest in the teaching of general pediatrics by giving national recognition to an outstanding general pediatric program. The PAS selection committee chose Children’s CHT for demonstrating excellence in educational teaching methods, acceptance by the community, its adaptability and the outstanding quality of residents trained in the program.

“As a community-focused health system, one of our central missions is to train a new generation of residents to create successful community partnerships and integrate public health concepts into the everyday practice of medicine to improve the health of underserved communities,” says Cara Lichtenstein, M.D., MPH and director of Children’s Community Health Track.

Children’s CHT focuses on underserved populations and the development of skills in health policy, advocacy and community healthcare delivery. Residents spend their outpatient time learning to use public health techniques to identify and address community health needs, becoming a physician advocate and learning more about the sociocultural determinants of health and health disparities. Training for CHT is integrated with Children’s overall pediatrics residency program to ensure excellence in attainment of clinical skills, and to allow residents the opportunity to work with Children’s top-rated primary care, specialty and hospital-based physicians and care teams.

This is the third time in recent years that Children’s National has been honored by the Academic Pediatric Association. In 2013, Mary Ottolini, M.D., MPH and vice chair of medical education was recognized for her leadership of Children’s Master Teacher Leadership Development program. In 2009, Denice Cora-Bramble, M.D., MBA accepted the APA Health Care Delivery Award for the Goldberg Center for Community Pediatric Health at Children’s National.

Children’s offers up to eight residency positions each year designated as Community Health Track positions. The goals of the track are centered on the core competencies of community pediatrics as described by the American Academy of Pediatrics. Primarily to train residents to:

Grasp the breadth of diversity inherent in the pediatric population and be familiar with health-related implications of cultural beliefs and practices of groups represented in the community.

Recognize the role of the pediatrician in identifying needs and facilitating access to resources for patients, families and communities.

Be aware of the risks to health and barriers to care for underserved children in Washington, D.C., and demonstrate skill in improving access to continuous comprehensive health maintenance.

Appreciate key issues related to the pediatrician’s role and interactions with local community agencies and advocacy groups.

Value the role of schools and childcare settings in supporting the educational and psychosocial development of children and adolescents.

Apply key principles about health promotion and disease prevention for children and adolescents over a set period of time.

Observe, interpret and report observations about the communities in which they serve.

The fundamental difference in this track compared to the more traditional Categorical Track lies in the outpatient experiences that occur in all three years of training. The CHT utilizes these outpatient experiences to help residents to attain a well-rounded community pediatrics experience.

“Washington, D.C. is an incredibly diverse community with large numbers of vulnerable children and families from D.C. and all over the world. Given our location in our nation’s capital, residents and faculty have the unique opportunity to work with national professional and advocacy organizations that are influencing policy – both locally and nationally – as it relates to children, families and health care,” says Mark Weissman, M.D., chief of general pediatrics and community health at Children’s National. “We’re thrilled to be recognized with the Academic Pediatric Association’s Teaching Program Award and grateful to Dr. Lichtenstein for her leadership and commitment to improving the health of D.C.’s children and training the next generation of pediatricians and advocates.”

The Children’s National Health System Fetal Medicine Institute hosted the 2nd annual International Symposium on the Fetal Brain in August 2017 in Washington, D.C.

Speakers at this year’s symposium focused on the following four areas:

Brain Development in an Unsupportive In Utero Environment – Diagnosis and Consequences

Supporting Brain Development in the Ex Utero Fetus: How Far Are We From Optimal?

Genomic and Epigenomic Mechanisms Underlying Differences in Brain Development

The Emergence of Consciousness and Pain Sensation

Adré J. du Plessis, M.B.Ch.B., M.P.H., Director of the Fetal Medicine Institute and Division Chief of Fetal and Transitional Medicine hosted the conference. In his opening remarks Dr. du Plessis noted “Our goal has been to gather together a diverse group from across the spectrum of disciplines focused on the well-being of the fetal brain and to engage all disciplines together.”

Diana Bianchi, MD gives her keynote presentation on non-invasive fetal testing at the second annual International Symposium on the Fetal Brain.

Invited, internationally renowned speakers presented on diverse topics, including Diana Bianchi, Director of the Eunice Kennedy Shriver National Institute of Child Health and Human Development who spoke on the “Non-Invasive Fetal Testing Beyond Karyotype: What’s in it for the Fetal Brain?”

A new component to the symposium was the clinically-focused breakfast breakout sessions, created based on feedback from attendees of the 2016 Symposium. Sessions covered varied topics such as “Fetal Ultrasound: the Cornerstone of Fetal Neurodiagnosis,” “The Essentials of Neurogenetic Testing,” “Developing a Transitional Fetal-Neonatal Program” and “Using MRI to Advance Fetal Neurodiagnosis.”

The conference started with an exciting discussion by Alistair Gunn, M.B.Ch.B., Head of the Department of Physiology at the University of Auckland. His presentation “Fetal Heart Rate: What It Does and Does Not Tell Us” explored the considerable body of evidence that essentially all decelerations are mediated by chemoreflex responses to repeated hypoxia and that the parasympathetic autonomic nervous system is the critical regulator of both fetal heart rate and heart rate variation in labor.

Data from the Association of American Medical Colleges on faculty promotion show a very low percentage of diverse assistant professors being promoted to associate professors, and a low percentage of diverse associate professors rising through the ranks to become full professors within academic medicine. Mary Ottolini, M.D., M.P.H., ME.d., vice chair for Medical Education at Children’s National Health System, professor of pediatrics at George Washington University School of Medicine and president of the Academic Pediatric Association (APA) addressed this problem at the recent Pediatric Academic Societies annual meeting. In her presentation, “APA approach to diversity-inclusion,” Dr. Ottolini explained various APA initiatives in place to assist underrepresented minority (URM) residents, fellows and junior faculty to advance academically in pediatric medicine.

The APA’s core value and strategic goal for diversity and inclusion is to increase diversity and engagement of its membership. To execute this initiative, New Century Scholars was created in 2004 as a national mentorship program to increase racial and ethnic diversity of academic pediatric medicine. The two-year program collaborates with the American Pediatric Society and utilizes junior and senior mentors to provide support to our URM residents with a special interest in health disparities, social determinants of health, cultural competency and minority child health and development.

Dr. Ottolini believes, “it’s important for our URM faculty to have early, strong mentorship that provides an idea of what it takes to be academically successful, by networking and collaborating with others.” She went on to say, “By forming these collaborations, they can transform an idea into a project that will be published, which strengthens their ability to achieve promotions.”

“Diversity and inclusion is an issue that is important for patients and the field of academic pediatrics because we need to have a physician workforce that resembles the patient population that we are entrusted to take care of,” Dr. Ottolini says.

Dr. Ottolini also explained APA’s current special interest groups were put in place to bring awareness to the role of race in the practice of medicine, and to provide resources by which members can support the healthy development and optimal care for U.S. youth of color. The ultimate goal is to develop strategies for increasing diversity and retention among academic medical faculty across the United States, and develop best practices for caring for youth of color in the primary care setting.

The presentation concluded with a question-and-answer session and further discussion from the audience. Since her presentation, Dr. Ottolini has received offers from other doctors and national organizations to fund these initiatives.

Today’s e-learning platforms are often static, one-way programs or web pages that ask passive users to read text or watch a video on screen. However, the emerging generation of e-learning features dynamic visualizations and interactions that immerse the user in real-time settings. Military pilots and vehicle operators, for example, still log hours in traditional ways, such as hands-on simulation and flight time, but now also sit in front of a computer and practice tackling unique scenarios designed to challenge and improve their real-time decision making under pressure.

In medical education, computer-based learning simulations and training modules have the promise to create “virtual patients,” giving trainees and physicians the opportunity for real-time evaluation and application of evidence-based care models. Mary Ottolini, M.D., M.P.H., M.Ed., vice chair of medical education and designated institutional official, and Jeff Sestokas, M.Ed., director of the E-Learning Center, are at the forefront of developing these types of training modules for a wide variety of users with variable experience and specialty/sub-specialty expertise in pediatric medicine.

Instructional technologists, multimedia developers and members of the Children’s Academy of Pediatric Educators (CAPE) – some of the nation’s best pediatric clinicians and medical educators – all work collaboratively to design programs that achieve specific educational goals. Each platform resides in a responsive template, making it accessible on a variety of devices and highly customizable to the needs of specific learners. A multitude of online communication and educational tactics are available to enhance learning, including live and archived lectures, forums, blogs, wikis, documents, training modules, virtual simulations, quizzes, podcasts and videoconferencing. Within each platform, individual educators have the ability to customize learning experiences even further, selecting specific modules and specialty content.

“We’re taking these tools to people where they are, and delivering the content in ways that really embrace how this latest generation of trainees receives and processes information,” says Sestokas.

Designed for Children’s National and sites around the country, the majority of the 25 plus platforms and portals created so far focus on what Children’s experts know best – the unique challenges and needs of pediatric patients and their families.

Mary Ottolini, M.D., M.P.H., M.Ed.

For example, clinical scenarios encompass more than simple clinical evaluation and diagnosis. The learning module BEARScalpel teaches surgical residents with limited prior exposure to pediatric care how to address common communication challenges that arise when interacting with pediatric patients and their families. Maybe the “digital” family has a language barrier or a child is in more grave condition than it appears and the trainee has to decide when and how to escalate the issue to an attending physician.

Another module asks participants to diagnose a three-dimensional nonverbal “digital” infant, based on visual and audio cues such as type of cry, skin tone and overall responsiveness.

This type of case-driven learning is relatively new in the universe of electronic medical education, but is showing early promise to improve students’ analytical thinking and problem solving skills.

“There is a lot of medical e-learning available,” Sestokas adds. “But not much e-learning is case-based. That’s something we’re doing that few others do, even in adult-focused medical education.”

A recently published study measured the success of one platform at achieving its educational goals. Participants had higher satisfaction, reported higher impact on knowledge and demonstrated higher scores on metrics assessing behavior change in a virtual environment when compared to the traditional format of reading. The results suggest that interactive modules are not only a preferred method of content delivery but also more likely to improve resident performance. This assessment was made possible by sophisticated tracking systems built into each platform. The data collection provides a steady stream of intelligence about user interaction with presentation format and content, and the material’s contribution to learning goals.

“These systems augment the long standing medical education practices of hands-on simulation and bedside patient care rotations, to allow us to expose trainees and physicians to more scenarios, more complications, and more challenging decisions. We know that the value of a trainee’s education is based on the quality of the cases they are exposed to,” says Dr. Ottolini. “Our goal is to equip these trainees with tools to care for pediatric patients in the future, but to also improve their ability to care for patients today, while they continue to learn.”

As a result of this innovative work, Children’s National is one of seven institutions, and the only children’s hospital, selected to receive an Accreditation Council for Graduate Medical Education (ACGME) Innovation Award that will develop next generation of learning resources for faculty and trainees around the country.

“We have the opportunity to ensure that we are doing the best possible job of training and continuously developing pediatric experts in a field that is rapidly changing and adapting,” concludes Dr. Ottolini. “The best way to do this is to develop flexible training systems that engage users, establish a habit of lifelong learning, and instill a desire for clinical care improvement.”

One patient-focused module creates a virtual grocery store to help patients
and families with celiac disease learn how to identify gluten-free food.

Critical white matter structures in the brains of babies born prematurely at low birth weight develop more robustly when their mothers breast-feed them, compared with preemies fed formula.

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Breast-feeding offers a slew of benefits to infants, including protection against common childhood infections and potentially reducing the risk of chronic health conditions such as asthma, obesity and type 2 diabetes. These benefits are especially important for infants born prematurely, or before 37 weeks gestation – a condition that affects 1 in 10 babies born in the United States, according to the Centers for Disease Control and Prevention. Prematurely born infants are particularly vulnerable to infections and other health problems.

Along with the challenges premature infants face, there is a heightened risk for neurodevelopmental disabilities that often do not fully emerge until the children enter school. A new study by Children’s National Health System researchers shows that breast-feeding might help with this problem. The findings, presented at the 2017 annual meeting of the Pediatric Academic Societies, show that critical white matter structures in the brains of babies born so early that they weigh less than 1,500 grams develop more robustly when their mothers breast-feed them, compared with preemie peers who are fed formula.

The Children’s National research team used sophisticated imaging tools to examine brain development in very low birth weight preemies, who weighed about 3 pounds at birth.

They enrolled 37 babies who were no more than 32 weeks gestational age at birth and were admitted to Children’s neonatal intensive care unit within the first 48 hours of life. Twenty-two of the preemies received formula specifically designed to meet the nutritional needs of infants born preterm, while 15 infants were fed breast milk. The researchers leveraged diffusion tensor imaging – which measures organization of the developing white matter of the brain – and 3-D volumetric magnetic resonance imaging (MRI) to calculate brain volume by region, structure and tissue type, such as cortical gray matter, white matter, deep gray matter and cerebellum.

“We did not find significant differences in the global and regional brain volumes when we conducted MRIs at 40 weeks gestation in both groups of prematurely born infants,” says Catherine Limperopoulos, Ph.D., director of the Developing Brain Research Laboratory and senior author of the paper. “There are striking differences in white matter microstructural organization, however, with greater fractional anisotropy in the left posterior limb of internal capsule and middle cerebellar peduncle, and lower mean diffusivity in the superior cerebellar peduncle.”

White matter lies under the gray matter cortex, makes up about half of the brain’s volume, and is a critical player in human development as well as in neurological disorders. The increased white matter microstructural organization in the cerebral and cerebellar white matter suggests more robust fiber tracts and microarchitecture of the developing white matter which may predict better neurologic outcomes in preterm infants. These critical structures that begin to form in the womb are used for the rest of the person’s life when, for instance, they attempt to master a new skill.

“Previous research has linked early breast milk feeding with increased volumetric brain growth and improved cognitive and behavioral outcomes,” she says. “These very vulnerable preemies already experience a high incidence rate of neurocognitive dysfunction – even if they do not have detectable structural brain injury. Providing them with breast milk early in life holds the potential to lessen those risks.”

The American Academy of Pediatrics endorses breast-feeding because it lowers infants’ chances of suffering from ear infections and diarrhea in the near term and decreases their risks of being obese as children. Limperopoulos says additional studies are needed in a larger group of patients as well as longer-term follow up as growing infants babble, scamper and color to gauge whether there are differences in motor skills, cognition and writing ability between the two groups.

Mary Ottolini, M.D., M.P.H., M.Ed., vice chair of medical education at Children’s National Health System and professor of pediatrics at The George Washington University, recently received the Council on Medical Student Education in Pediatrics (COMSEP) Achievement Award during the group’s annual meeting in Portland, Oregon. This prestigious award is given to a current or former COMSEP member who has made major contributions to the organization and its members.

Since joining the organization in 2000, Dr. Ottolini has become a leader in the COMSEP Education Technology task force, a mentor to medical students, a teacher in clinical settings and an education innovator. Currently, Dr. Ottolini’s work with COMSEP is focused on overturning a Centers for Medicare & Medicaid Services regulation that bars medical students from documenting in the medical record, which interferes with their progress to becoming physicians. She continues to uphold the educational mission of Children’s National in caring for children by training the pediatric experts of tomorrow.

New research shows the effectiveness of an Advance Care Planning model developed through participatory research with adolescents in improving palliative care among adult people living with #HIV
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